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从 hPSC 视网膜类器官中分离的 CD29/CD44 细胞的转录组学分析揭示了具有视网膜祖细胞和 Müller 胶质细胞特征的单一细胞群体。

Transcriptomics of CD29/CD44 cells isolated from hPSC retinal organoids reveals a single cell population with retinal progenitor and Müller glia characteristics.

机构信息

NIHR Biomedical Research Centre at Moorfields Eye Hospital, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL, UK.

出版信息

Sci Rep. 2023 Mar 28;13(1):5081. doi: 10.1038/s41598-023-32058-w.

Abstract

Müller glia play very important and diverse roles in retinal homeostasis and disease. Although much is known of the physiological and morphological properties of mammalian Müller glia, there is still the need to further understand the profile of these cells during human retinal development. Using human embryonic stem cell-derived retinal organoids, we investigated the transcriptomic profiles of CD29/CD44 cells isolated from early and late stages of organoid development. Data showed that these cells express classic markers of retinal progenitors and Müller glia, including NFIX, RAX, PAX6, VSX2, HES1, WNT2B, SOX, NR2F1/2, ASCL1 and VIM, as early as days 10-20 after initiation of retinal differentiation. Expression of genes upregulated in CD29/CD44 cells isolated at later stages of organoid development (days 50-90), including NEUROG1, VSX2 and ASCL1 were gradually increased as retinal organoid maturation progressed. Based on the current observations that CD24/CD44 cells share the characteristics of early and late-stage retinal progenitors as well as of mature Müller glia, we propose that these cells constitute a single cell population that upon exposure to developmental cues regulates its gene expression to adapt to functions exerted by Müller glia in the postnatal and mature retina.

摘要

Müller 胶质细胞在视网膜稳态和疾病中发挥着非常重要和多样化的作用。尽管人们对哺乳动物 Müller 胶质细胞的生理和形态特性有了很多了解,但仍有必要进一步了解人类视网膜发育过程中这些细胞的特征。我们使用人类胚胎干细胞衍生的视网膜类器官,研究了从类器官发育早期和晚期分离的 CD29/CD44 细胞的转录组谱。数据表明,这些细胞表达视网膜祖细胞和 Müller 胶质细胞的经典标志物,包括 NFIX、RAX、PAX6、VSX2、HES1、WNT2B、SOX、NR2F1/2、ASCL1 和 VIM,早在视网膜分化开始后的 10-20 天。在类器官发育后期(第 50-90 天)分离的 CD29/CD44 细胞中上调的基因表达,包括 NEUROG1、VSX2 和 ASCL1,随着视网膜类器官的成熟而逐渐增加。基于目前的观察结果,即 CD24/CD44 细胞具有早期和晚期视网膜祖细胞以及成熟 Müller 胶质细胞的特征,我们提出这些细胞构成了一个单一的细胞群体,当暴露于发育信号时,它会调节其基因表达以适应 Müller 胶质细胞在出生后和成熟视网膜中发挥的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3e3/10050419/65fd392eea00/41598_2023_32058_Fig1_HTML.jpg

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